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Bevacizumab With or Without TRC105 in Treating Patients With Metastatic Kidney Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01727089
Collaborator
(none)
59
Enrollment
30
Locations
2
Arms
57.2
Actual Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well bevacizumab with or without anti-endoglin monoclonal antibody TRC105 (TRC105) works in treating patients with kidney cancer that has spread to other parts of the body (metastatic). Monoclonal antibodies, such as bevacizumab and anti-endoglin monoclonal antibody TRC105, may block tumor growth in different ways by targeting certain cells.

Condition or Disease Intervention/Treatment Phase
  • Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105
  • Biological: Bevacizumab
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
 Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To compare the progression-free survival at 12 and 24 weeks for bevacizumab alone or in combination with TRC105 (anti-endoglin monoclonal antibody TRC105).
SECONDARY OBJECTIVES:
  1. Toxicity and Response Evaluation Criteria in Solid Tumors (RECIST) response rate for the combination compared to single agent bevacizumab.
TERTIARY OBJECTIVES:

  1. To evaluate tumor tissue expression of endoglin (CD105), transforming growth factor, beta receptor II (TGFBR2), activin A receptor type II-like 1 (ACVRL1) and transforming growth factor, beta receptor 1 (TGFBR1) kinase from pre- and post-treatment tissue samples in order to determine whether CD105 and stem cell activation occurs after exposure to anti-vascular endothelial growth factor (VEGF) therapy as predicted by laboratory models, and whether exposure to anti-endoglin monoclonal antibody TRC105 affects these changes.

  2. To compare the soluble CD105 levels at baseline and after treatment between the group receiving bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin monoclonal antibody TRC105.

  3. To compare TGFBR2 levels at baseline and after treatment between the group receiving bevacizumab alone and the group receiving bevacizumab in combination with anti-endoglin monoclonal antibody TRC105.

  4. To evaluate whether circulating tumor cells (CTCs) can be detected in this patient population using parylene membrane filter technology, and whether changes in CTC counts and CD105 expression on CTCs during therapy correspond to imaging and clinical response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15.

ARM II: Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 1, 8, 15, and 22.

In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 4 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
59 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Bevacizumab Alone or in Combination With TRC105 for Advanced Renal Cell Cancer
Actual Study Start Date :
Nov 1, 2012
Actual Primary Completion Date :
Aug 8, 2017
Actual Study Completion Date :
Aug 8, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I (bevacizumab)

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab
Given IV
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar FKB238
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF

    • Other: Laboratory Biomarker Analysis
    Correlative studies
    Experimental: Arm II (bevacizumab, anti-endoglin monoclonal antibody TRC105)

    Patients receive bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

    Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105
    Given IV
    Other Names:
  • TRC105

    • Biological: Bevacizumab
    Given IV
    Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar CBT 124
  • Bevacizumab Biosimilar FKB238
  • Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
  • Recombinant Humanized Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF

    • Other: Laboratory Biomarker Analysis
    Correlative studies

    Other: Pharmacological Study
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival at 24 Weeks [The duration of time from start of treatment to time of progression or death, assessed at 24 weeks]

      Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    2. Progression-free Survival at 12 Weeks [The duration of time from start of treatment to time of progression or death, assessed at 12 weeks]

      Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Secondary Outcome Measures

    1. Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment [From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.]

      The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting. Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.

    2. Number of Participants With Overall Response [From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients must have histologically or cytologically confirmed renal cancer; all histologic subtypes will be eligible

    • Patients must have metastatic disease which is measurable, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) to >= 20 mm in the long axis by chest x-ray, >= 10 mm in the long axis by spiral computed tomography (CT), magnetic resonance imaging (MRI), calipers, or clinical exam, or >= 15 mm in the short axis for lymph nodes

    • Patients must have received at least 1 prior systemic therapy for renal cancer but no more than 4 prior therapies; they must have documented intolerance to or progression despite at least 1 systemic therapy; therapy administered in the adjuvant setting counts toward the prior systemic therapy total; if adjuvant therapy is the patient's only prior therapy the disease must have recurred during treatment or within 3 months of discontinuation

    • Allowable prior therapies include VEGF tyrosine kinase inhibitor (TKIs), mammalian target of rapamycin (mTOR) inhibitors, and cytokine therapy (example: interleukin-2 [IL2])

    • At least 2 weeks must have elapsed from the last dose of the prior systemic therapy for biologics and 4 weeks for chemotherapy (6 weeks for nitrosoureas or mitomycin C); also note that at least 3 weeks should have elapsed since prior TKI administration

    • Eastern Cooperative Oncology Group (ECOG) performance status =< 2

    • Life expectancy of greater than 6 months

    • Leukocytes >= 3,000/mcL

    • Absolute neutrophil count >= 1,500/mcL

    • Platelets >= 100,000/mcL

    • Total bilirubin =< institutional upper limits or normal (except for Gilbert's)

    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (except subjects with liver metastases, who can have AST/ALT =< 5 x ULN)

    • Creatinine glomerular filtration rate (GFR) (calculated or measured) > 50 mL/min

    • Hemoglobin >= 9 g/dL

    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of TRC105 or bevacizumab administration

    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Patients who have had systemic biologic therapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events related to their prior therapy

    • Patients who have previously been treated with bevacizumab

    • Patients who have previously been treated with TRC105

    • Patients who are receiving any other investigational agents

    • Known central nervous system (CNS) disease except for treated brain metastasis; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (MRI or CT) (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC105 or bevacizumab

    • Patients on full-dose anticoagulation will be excluded; antiplatelet therapy will not be exclusionary

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unhealed wound, gastrointestinal fistula, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction, cerebrovascular accident

    • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother wishes to participate in the study

    • Patients with a history of bleeding diathesis or inherited coagulopathy are excluded; in addition, those with a history of deep vein thrombosis (DVT) or pulmonary embolus within 1 year and still requiring active anticoagulation will be excluded; those with a more remote history of DVT or pulmonary embolus may be eligible but the risk of recurrent thrombosis should be considered

    • Patients with history of hereditary hemorrhagic telangiectasis (HHT-1 and HHT-2)

    • Serious or non-healing wound, ulcer, or bone fracture OR history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

    • Invasive procedures defined as follows:

    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy

    • Anticipation of need for major surgical procedures during the course of the study

    • Core biopsy within 7 days prior to day 1 therapy

    • Patients with clinically significant cardiovascular disease are excluded:

    • Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 160 mmHg and/or diastolic blood pressure [DBP] > 90 mmHg despite antihypertensive medication)

    • History of cerebrovascular accident (CVA) within 6 months

    • Myocardial infarction or unstable angina within 6 months

    • New York Heart Association grade II or greater congestive heart failure

    • Serious and inadequately controlled cardiac arrhythmia

    • Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)

    • Clinically significant peripheral vascular disease

    • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

    • Patients with psychiatric illness/social situations that would limit compliance with study requirements will be excluded

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 USC / Norris Comprehensive Cancer Center Los Angeles California United States 90033
    3 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    4 City of Hope South Pasadena South Pasadena California United States 91030
    5 University of Colorado Cancer Center - Anschutz Cancer Pavilion Aurora Colorado United States 80045
    6 University of Colorado Denver Colorado United States 80217-3364
    7 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    8 Moffitt Cancer Center Tampa Florida United States 33612
    9 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    10 Decatur Memorial Hospital Decatur Illinois United States 62526
    11 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    12 NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois United States 60026
    13 Ingalls Memorial Hospital Harvey Illinois United States 60426
    14 Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard Fort Wayne Indiana United States 46804
    15 Fort Wayne Medical Oncology and Hematology Inc-Parkview Fort Wayne Indiana United States 46845
    16 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    17 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    18 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    19 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    20 Mayo Clinic Rochester Minnesota United States 55905
    21 Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota United States 55416
    22 Washington University School of Medicine Saint Louis Missouri United States 63110
    23 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    24 Penn State Milton S Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    25 University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania United States 15232
    26 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    27 M D Anderson Cancer Center Houston Texas United States 77030
    28 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    29 Royal Prince Alfred Hospital Camperdown New South Wales Australia 2050
    30 National Taiwan University Hospital Taipei Taiwan 100

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Tanya Dorff, City of Hope Comprehensive Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01727089
    Other Study ID Numbers:
    • NCI-2012-02206
    • NCI-2012-02206
    • PHII-121
    • PhII-121
    • 9144
    • N01CM00038
    • N01CM00039
    • N01CM00071
    • N01CM00099
    • P30CA033572
    First Posted:
    Nov 15, 2012
    Last Update Posted:
    Aug 28, 2018
    Last Verified:
    Jul 1, 2018
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Renal Cell
    Bevacizumab
    Antineoplastic Agents, Immunological
    Endothelial Growth Factors
    Antibodies
    Immunoglobulins
    Antibodies, Monoclonal
    Immunoglobulin G

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
    Period Title: Overall Study
    STARTED 29 30
    COMPLETED 29 30
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105) Total
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Total of all reporting groups
    Overall Participants 29 30 59
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    58
    65
    60
    Sex: Female, Male (Count of Participants)
    Female
    9
    31%
    6
    20%
    15
    25.4%
    Male
    20
    69%
    24
    80%
    44
    74.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    24.1%
    3
    10%
    10
    16.9%
    Not Hispanic or Latino
    22
    75.9%
    27
    90%
    49
    83.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    3
    10.3%
    0
    0%
    3
    5.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    6.9%
    2
    6.7%
    4
    6.8%
    White
    24
    82.8%
    28
    93.3%
    52
    88.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    29
    100%
    30
    100%
    59
    100%

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival at 24 Weeks
    Description Progression-free survival 24 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame The duration of time from start of treatment to time of progression or death, assessed at 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
    Measure Participants 29 30
    Number (95% Confidence Interval) [percentage of participants]
    52
    179.3%
    27
    90%
    2. Primary Outcome
    Title Progression-free Survival at 12 Weeks
    Description Progression-free survival 12 after starting treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame The duration of time from start of treatment to time of progression or death, assessed at 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
    Measure Participants 29 30
    Number (95% Confidence Interval) [percentage of participants]
    66
    227.6%
    58
    193.3%
    3. Secondary Outcome
    Title Number of Participants With Grade 3 and Above Adverse Events (AE) Related to Treatment
    Description The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for AE reporting. Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related adverse event.
    Time Frame From time of treatment initiation until 30 days post treatment, assessed every 4 weeks.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
    Measure Participants 29 30
    Abdominal pain
    3
    10.3%
    3
    10%
    Anemia
    4
    13.8%
    8
    26.7%
    Anorexia
    0
    0%
    1
    3.3%
    Bleeding
    2
    6.9%
    0
    0%
    bronchopulmonary hemorrhage
    1
    3.4%
    0
    0%
    Fatigue
    0
    0%
    2
    6.7%
    Hypercalcemia
    0
    0%
    2
    6.7%
    Hypertension
    5
    17.2%
    4
    13.3%
    Hyponatremia
    1
    3.4%
    2
    6.7%
    Infusion reaction
    0
    0%
    2
    6.7%
    Nausea/vomitting
    0
    0%
    5
    16.7%
    Proteinuria
    2
    6.9%
    0
    0%
    4. Secondary Outcome
    Title Number of Participants With Overall Response
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
    Time Frame From time of treatment initiation until conclusion of treatment, assessed every 12 weeks.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
    Measure Participants 29 30
    Number [participants]
    1
    3.4%
    1
    3.3%

    Adverse Events

    Time Frame Adverse events occurred over a period of 2 years and 7 months.
    Adverse Event Reporting Description "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
    Arm/Group Title Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Arm/Group Description Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Patients receive 10 mg\kg bevacizumab as in Arm I and anti-endoglin monoclonal antibody TRC105 10 mg\kg IV over 1-4 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Anti-Endoglin Chimeric Monoclonal Antibody TRC105: Given IV Bevacizumab: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
    All Cause Mortality
    Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/29 (13.8%) 5/30 (16.7%)
    Serious Adverse Events
    Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/29 (34.5%) 14/30 (46.7%)
    Blood and lymphatic system disorders
    Anemia 0/29 (0%) 0 1/30 (3.3%) 1
    Cardiac disorders
    Heart failure 2/29 (6.9%) 3 0/30 (0%) 0
    Left ventricular systolic dysfunction 1/29 (3.4%) 2 0/30 (0%) 0
    Restrictive cardiomyopathy 1/29 (3.4%) 2 0/30 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/29 (0%) 0 2/30 (6.7%) 2
    Ascites 0/29 (0%) 0 1/30 (3.3%) 1
    Constipation 0/29 (0%) 0 1/30 (3.3%) 1
    Duodenal hemorrhage 1/29 (3.4%) 1 0/30 (0%) 0
    Ileus 0/29 (0%) 0 1/30 (3.3%) 1
    Nausea 0/29 (0%) 0 1/30 (3.3%) 1
    Pancreatitis 1/29 (3.4%) 1 0/30 (0%) 0
    Vomiting 0/29 (0%) 0 3/30 (10%) 3
    General disorders
    Death NOS 0/29 (0%) 0 1/30 (3.3%) 1
    Edema limbs 0/29 (0%) 0 1/30 (3.3%) 1
    Failure to thrive 0/29 (0%) 0 1/30 (3.3%) 1
    Fatigue 0/29 (0%) 0 2/30 (6.7%) 2
    Fever 1/29 (3.4%) 2 0/30 (0%) 0
    Infusion related reaction 0/29 (0%) 0 1/30 (3.3%) 1
    Pain 2/29 (6.9%) 2 0/30 (0%) 0
    Weakness 0/29 (0%) 0 1/30 (3.3%) 1
    Hepatobiliary disorders
    Bile duct stenosis 0/29 (0%) 0 1/30 (3.3%) 1
    Hepatic failure 0/29 (0%) 0 1/30 (3.3%) 1
    Infections and infestations
    Lung infection 0/29 (0%) 0 1/30 (3.3%) 1
    Skin infection 1/29 (3.4%) 1 0/30 (0%) 0
    Urinary tract infection 0/29 (0%) 0 2/30 (6.7%) 2
    Injury, poisoning and procedural complications
    Fall 1/29 (3.4%) 1 0/30 (0%) 0
    Investigations
    Aspartate aminotransferase increased 0/29 (0%) 0 1/30 (3.3%) 1
    Creatinine increased 1/29 (3.4%) 1 0/30 (0%) 0
    Lymphocyte count decreased 0/29 (0%) 0 1/30 (3.3%) 2
    progression of renal cell cancer 0/29 (0%) 0 1/30 (3.3%) 1
    Metabolism and nutrition disorders
    Anorexia 0/29 (0%) 0 1/30 (3.3%) 1
    Dehydration 1/29 (3.4%) 1 1/30 (3.3%) 1
    Hypercalcemia 0/29 (0%) 0 2/30 (6.7%) 2
    Hyperkalemia 1/29 (3.4%) 2 1/30 (3.3%) 1
    Hyponatremia 0/29 (0%) 0 1/30 (3.3%) 3
    Hypophosphatemia 0/29 (0%) 0 1/30 (3.3%) 1
    Musculoskeletal and connective tissue disorders
    Bone pain 1/29 (3.4%) 1 1/30 (3.3%) 1
    Flank pain 0/29 (0%) 0 1/30 (3.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Disease progression 0/29 (0%) 0 1/30 (3.3%) 1
    Progressive Disease 0/29 (0%) 0 1/30 (3.3%) 1
    death 1/29 (3.4%) 1 0/30 (0%) 0
    Nervous system disorders
    Presyncope 1/29 (3.4%) 1 0/30 (0%) 0
    Somnolence 1/29 (3.4%) 1 0/30 (0%) 0
    Syncope 1/29 (3.4%) 1 0/30 (0%) 0
    Psychiatric disorders
    Anxiety 1/29 (3.4%) 1 0/30 (0%) 0
    Confusion 1/29 (3.4%) 1 0/30 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 1/29 (3.4%) 2 0/30 (0%) 0
    Chronic kidney disease 1/29 (3.4%) 2 0/30 (0%) 0
    Proteinuria 1/29 (3.4%) 1 0/30 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Bronchopulmonary hemorrhage 1/29 (3.4%) 1 0/30 (0%) 0
    Dyspnea 3/29 (10.3%) 4 3/30 (10%) 3
    Hypoxia 0/29 (0%) 0 1/30 (3.3%) 1
    Pleural effusion 0/29 (0%) 0 2/30 (6.7%) 2
    Productive cough 1/29 (3.4%) 1 0/30 (0%) 0
    Skin and subcutaneous tissue disorders
    Bullous dermatitis 0/29 (0%) 0 1/30 (3.3%) 1
    scalp laceration 1/29 (3.4%) 1 0/30 (0%) 0
    Vascular disorders
    Hypertension 1/29 (3.4%) 1 2/30 (6.7%) 13
    Hypotension 0/29 (0%) 0 1/30 (3.3%) 1
    Other (Not Including Serious) Adverse Events
    Arm I (Bevacizumab) Arm II (Bevacizumab, Anti-endoglin Monoclonal Antibody TRC105)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 29/29 (100%) 29/30 (96.7%)
    Blood and lymphatic system disorders
    Anemia 10/29 (34.5%) 29 16/30 (53.3%) 79
    Cardiac disorders
    Sinus bradycardia 3/29 (10.3%) 11 5/30 (16.7%) 9
    Sinus tachycardia 1/29 (3.4%) 1 5/30 (16.7%) 13
    Ear and labyrinth disorders
    Ear pain 1/29 (3.4%) 1 0/30 (0%) 0
    Vertigo 2/29 (6.9%) 2 0/30 (0%) 0
    Eye disorders
    Blurred vision 1/29 (3.4%) 1 2/30 (6.7%) 2
    Glaucoma 1/29 (3.4%) 1 1/30 (3.3%) 1
    Itchy Eyes 0/29 (0%) 0 1/30 (3.3%) 1
    Watering eyes 0/29 (0%) 0 1/30 (3.3%) 1
    suconjunctival hemorrhage 0/29 (0%) 0 1/30 (3.3%) 1
    Gastrointestinal disorders
    Abdominal distension 2/29 (6.9%) 3 2/30 (6.7%) 6
    Abdominal pain 8/29 (27.6%) 11 4/30 (13.3%) 14
    Ascites 0/29 (0%) 0 1/30 (3.3%) 1
    Bloating 2/29 (6.9%) 3 1/30 (3.3%) 1
    Blood in Stool 1/29 (3.4%) 1 0/30 (0%) 0
    Constipation 8/29 (27.6%) 13 8/30 (26.7%) 10
    Diarrhea 4/29 (13.8%) 6 7/30 (23.3%) 7
    Dry mouth 1/29 (3.4%) 1 3/30 (10%) 3
    Duodenal hemorrhage 1/29 (3.4%) 1 0/30 (0%) 0
    Dyspepsia 1/29 (3.4%) 1 0/30 (0%) 0
    Dysphagia 1/29 (3.4%) 1 0/30 (0%) 0
    Flatulence 0/29 (0%) 0 1/30 (3.3%) 2
    Gastric hemorrhage 1/29 (3.4%) 1 0/30 (0%) 0
    Gastroesophageal reflux disease 1/29 (3.4%) 2 1/30 (3.3%) 1
    Gingival pain 0/29 (0%) 0 2/30 (6.7%) 3
    Mucositis oral 2/29 (6.9%) 6 1/30 (3.3%) 1
    Nausea 7/29 (24.1%) 9 10/30 (33.3%) 16
    Oral dysesthesia 0/29 (0%) 0 1/30 (3.3%) 1
    Oral hemorrhage 0/29 (0%) 0 4/30 (13.3%) 17
    Oral pain 1/29 (3.4%) 2 1/30 (3.3%) 1
    Periodontal disease 0/29 (0%) 0 1/30 (3.3%) 1
    Rectal discharge 1/29 (3.4%) 1 0/30 (0%) 0
    Rectal hemorrhage 0/29 (0%) 0 1/30 (3.3%) 1
    Stomach pain 1/29 (3.4%) 1 0/30 (0%) 0
    Tongue Ulcerations 0/29 (0%) 0 1/30 (3.3%) 1
    Vomiting 4/29 (13.8%) 4 7/30 (23.3%) 9
    diverticulosis 1/29 (3.4%) 1 0/30 (0%) 0
    hiatal hernia 1/29 (3.4%) 1 0/30 (0%) 0
    General disorders
    Bloody Gums 0/29 (0%) 0 1/30 (3.3%) 1
    Chills 4/29 (13.8%) 6 2/30 (6.7%) 5
    Cracked Lips 0/29 (0%) 0 1/30 (3.3%) 1
    Death NOS 1/29 (3.4%) 1 0/30 (0%) 0
    Edema limbs 4/29 (13.8%) 4 5/30 (16.7%) 6
    Fatigue 18/29 (62.1%) 54 23/30 (76.7%) 79
    Fever 4/29 (13.8%) 5 3/30 (10%) 3
    Flu like symptoms 1/29 (3.4%) 1 1/30 (3.3%) 1
    Increased Thirst 0/29 (0%) 0 1/30 (3.3%) 1
    Infusion related reaction 1/29 (3.4%) 1 5/30 (16.7%) 6
    Localized edema 1/29 (3.4%) 1 0/30 (0%) 0
    Malaise 1/29 (3.4%) 1 0/30 (0%) 0
    Night sweats 1/29 (3.4%) 1 0/30 (0%) 0
    Non-cardiac chest pain 1/29 (3.4%) 1 3/30 (10%) 4
    Pain 2/29 (6.9%) 7 7/30 (23.3%) 11
    Rash 0/29 (0%) 0 1/30 (3.3%) 1
    Swelling of Feet 0/29 (0%) 0 1/30 (3.3%) 1
    swelling of feet 0/29 (0%) 0 1/30 (3.3%) 2
    Infections and infestations
    Sinusitis 1/29 (3.4%) 1 1/30 (3.3%) 1
    Skin infection 2/29 (6.9%) 2 3/30 (10%) 4
    Upper respiratory infection 1/29 (3.4%) 2 1/30 (3.3%) 1
    Urinary tract infection 1/29 (3.4%) 1 2/30 (6.7%) 2
    Injury, poisoning and procedural complications
    Bruising 0/29 (0%) 0 2/30 (6.7%) 14
    Fall 1/29 (3.4%) 1 1/30 (3.3%) 1
    Investigations
    Activated partial thromboplastin time pr 2/29 (6.9%) 2 1/30 (3.3%) 1
    Alanine aminotransferase increased 7/29 (24.1%) 26 3/30 (10%) 5
    Alkaline phosphatase increased 7/29 (24.1%) 13 6/30 (20%) 11
    Aspartate aminotransferase increased 6/29 (20.7%) 17 7/30 (23.3%) 9
    Blood bilirubin increased 1/29 (3.4%) 1 3/30 (10%) 3
    Cardiac troponin T increased 1/29 (3.4%) 1 0/30 (0%) 0
    Cholesterol high 1/29 (3.4%) 2 0/30 (0%) 0
    Creatinine increased 7/29 (24.1%) 15 6/30 (20%) 14
    Elevated BUN 2/29 (6.9%) 2 0/30 (0%) 0
    Elevated BUN count 1/29 (3.4%) 1 0/30 (0%) 0
    Elevated Eos Auto 1/29 (3.4%) 1 0/30 (0%) 0
    Elevated LDH 1/29 (3.4%) 3 0/30 (0%) 0
    GGT increased 1/29 (3.4%) 6 0/30 (0%) 0
    Hemoglobin increased 1/29 (3.4%) 6 0/30 (0%) 0
    INCREASED LDH 1/29 (3.4%) 3 0/30 (0%) 0
    INR increased 1/29 (3.4%) 3 1/30 (3.3%) 1
    Lipase increased 1/29 (3.4%) 1 0/30 (0%) 0
    Low Co2 0/29 (0%) 0 1/30 (3.3%) 2
    Low LDH 1/29 (3.4%) 2 0/30 (0%) 0
    Low chloride count 1/29 (3.4%) 3 0/30 (0%) 0
    Lymphocyte count decreased 1/29 (3.4%) 1 4/30 (13.3%) 7
    Lymphocyte count increased 0/29 (0%) 0 1/30 (3.3%) 2
    Platelet count decreased 6/29 (20.7%) 22 3/30 (10%) 4
    Weight gain 2/29 (6.9%) 3 5/30 (16.7%) 22
    Weight loss 3/29 (10.3%) 7 4/30 (13.3%) 9
    White blood cell decreased 1/29 (3.4%) 1 0/30 (0%) 0
    creatinine increased 0/29 (0%) 0 1/30 (3.3%) 1
    Metabolism and nutrition disorders
    Anorexia 9/29 (31%) 19 9/30 (30%) 15
    Dehydration 2/29 (6.9%) 2 7/30 (23.3%) 8
    GLUCOSURIA 1/29 (3.4%) 2 0/30 (0%) 0
    Glucose intolerance 1/29 (3.4%) 1 0/30 (0%) 0
    Hypercalcemia 4/29 (13.8%) 7 3/30 (10%) 3
    Hyperglycemia 6/29 (20.7%) 18 8/30 (26.7%) 35
    Hyperkalemia 7/29 (24.1%) 16 9/30 (30%) 13
    Hypermagnesemia 1/29 (3.4%) 1 3/30 (10%) 3
    Hypernatremia 3/29 (10.3%) 6 4/30 (13.3%) 4
    Hypertriglyceridemia 1/29 (3.4%) 4 0/30 (0%) 0
    Hypoalbuminemia 10/29 (34.5%) 21 8/30 (26.7%) 28
    Hypocalcemia 4/29 (13.8%) 5 4/30 (13.3%) 6
    Hypoglycemia 5/29 (17.2%) 7 4/30 (13.3%) 4
    Hypokalemia 1/29 (3.4%) 1 4/30 (13.3%) 6
    Hypomagnesemia 0/29 (0%) 0 1/30 (3.3%) 1
    Hyponatremia 11/29 (37.9%) 25 11/30 (36.7%) 29
    Hypophosphatemia 0/29 (0%) 0 1/30 (3.3%) 1
    Obesity 3/29 (10.3%) 5 3/30 (10%) 10
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/29 (13.8%) 4 3/30 (10%) 7
    Arthritis 0/29 (0%) 0 1/30 (3.3%) 1
    Back pain 8/29 (27.6%) 10 7/30 (23.3%) 11
    Bone pain 4/29 (13.8%) 5 0/30 (0%) 0
    Chest wall pain 1/29 (3.4%) 1 4/30 (13.3%) 7
    Generalized muscle weakness 1/29 (3.4%) 1 1/30 (3.3%) 2
    Intermittent Chest Wall Tenderness 0/29 (0%) 0 1/30 (3.3%) 1
    Joint range of motion decreased 1/29 (3.4%) 1 0/30 (0%) 0
    Muscle Cramps 0/29 (0%) 0 1/30 (3.3%) 1
    Myalgia 2/29 (6.9%) 2 1/30 (3.3%) 1
    Neck pain 3/29 (10.3%) 4 0/30 (0%) 0
    Pain in extremity 3/29 (10.3%) 7 3/30 (10%) 3
    Scoliosis 0/29 (0%) 0 1/30 (3.3%) 1
    anterolisthesis 0/29 (0%) 0 1/30 (3.3%) 1
    lumbar disk degeneration 0/29 (0%) 0 1/30 (3.3%) 1
    Nervous system disorders
    Cognitive disturbance 0/29 (0%) 0 1/30 (3.3%) 1
    Concentration impairment 0/29 (0%) 0 1/30 (3.3%) 1
    Dizziness 5/29 (17.2%) 7 5/30 (16.7%) 10
    Dysarthria 0/29 (0%) 0 2/30 (6.7%) 2
    Dysgeusia 0/29 (0%) 0 1/30 (3.3%) 1
    Headache 10/29 (34.5%) 22 15/30 (50%) 25
    Lethargy 0/29 (0%) 0 1/30 (3.3%) 2
    Paresthesia 1/29 (3.4%) 2 2/30 (6.7%) 4
    Peripheral motor neuropathy 0/29 (0%) 0 1/30 (3.3%) 1
    Peripheral sensory neuropathy 1/29 (3.4%) 3 2/30 (6.7%) 2
    Presyncope 0/29 (0%) 0 1/30 (3.3%) 1
    Rigors 0/29 (0%) 0 1/30 (3.3%) 1
    Sinus pain 1/29 (3.4%) 1 1/30 (3.3%) 9
    Somnolence 1/29 (3.4%) 1 0/30 (0%) 0
    Tremor 0/29 (0%) 0 1/30 (3.3%) 1
    Psychiatric disorders
    Anxiety 1/29 (3.4%) 2 3/30 (10%) 3
    Confusion 1/29 (3.4%) 1 3/30 (10%) 3
    Depression 1/29 (3.4%) 1 1/30 (3.3%) 1
    Insomnia 2/29 (6.9%) 2 4/30 (13.3%) 4
    Renal and urinary disorders
    Burning sensation in urine 1/29 (3.4%) 1 0/30 (0%) 0
    Chronic kidney disease 0/29 (0%) 0 1/30 (3.3%) 1
    Hematuria 4/29 (13.8%) 8 2/30 (6.7%) 2
    Hemoglobinuria 0/29 (0%) 0 1/30 (3.3%) 1
    Hyaline casts >2 1/29 (3.4%) 1 0/30 (0%) 0
    Leukocyte Esterase 3+ 1/29 (3.4%) 1 0/30 (0%) 0
    Proteinuria 11/29 (37.9%) 43 8/30 (26.7%) 20
    RBC's > 50 1/29 (3.4%) 1 0/30 (0%) 0
    Urinary fistula 1/29 (3.4%) 1 0/30 (0%) 0
    Urinary frequency 2/29 (6.9%) 3 1/30 (3.3%) 1
    Urinary incontinence 0/29 (0%) 0 1/30 (3.3%) 2
    Urinary retention 1/29 (3.4%) 1 0/30 (0%) 0
    Urinary urgency 0/29 (0%) 0 1/30 (3.3%) 1
    Urine discoloration 1/29 (3.4%) 1 0/30 (0%) 0
    WBC's > 50 1/29 (3.4%) 1 0/30 (0%) 0
    pneumaturia 1/29 (3.4%) 1 0/30 (0%) 0
    Reproductive system and breast disorders
    Vaginal hemorrhage 0/29 (0%) 0 1/30 (3.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/29 (0%) 0 3/30 (10%) 3
    Bradypnea 0/29 (0%) 0 1/30 (3.3%) 1
    Cough 8/29 (27.6%) 10 7/30 (23.3%) 11
    Dyspnea 4/29 (13.8%) 8 9/30 (30%) 19
    Epistaxis 3/29 (10.3%) 8 16/30 (53.3%) 56
    Hoarseness 2/29 (6.9%) 4 3/30 (10%) 7
    Laryngeal hemorrhage 1/29 (3.4%) 3 1/30 (3.3%) 1
    Nasal congestion 2/29 (6.9%) 2 0/30 (0%) 0
    Pleural effusion 0/29 (0%) 0 2/30 (6.7%) 2
    Pleuritic pain 0/29 (0%) 0 1/30 (3.3%) 2
    Productive cough 0/29 (0%) 0 1/30 (3.3%) 1
    Pulmonary hypertension 0/29 (0%) 0 1/30 (3.3%) 1
    Sneezing 0/29 (0%) 0 1/30 (3.3%) 1
    Sore throat 2/29 (6.9%) 3 1/30 (3.3%) 7
    Tachypnea 0/29 (0%) 0 1/30 (3.3%) 1
    Wheezing 0/29 (0%) 0 1/30 (3.3%) 4
    congestion 0/29 (0%) 0 1/30 (3.3%) 1
    hemoptysis 1/29 (3.4%) 1 1/30 (3.3%) 1
    nose bleed 0/29 (0%) 0 1/30 (3.3%) 1
    Skin and subcutaneous tissue disorders
    ABRASION LEFT HAND 1/29 (3.4%) 1 0/30 (0%) 0
    Alopecia 1/29 (3.4%) 1 0/30 (0%) 0
    Dry skin 0/29 (0%) 0 2/30 (6.7%) 2
    Face and Scalp Skin Lesions 0/29 (0%) 0 1/30 (3.3%) 1
    Face and scalp lesions 0/29 (0%) 0 1/30 (3.3%) 1
    Hyperhidrosis 4/29 (13.8%) 4 1/30 (3.3%) 1
    Nail ridging 1/29 (3.4%) 1 1/30 (3.3%) 1
    Neck rash 0/29 (0%) 0 1/30 (3.3%) 1
    Palmar-plantar erythrodysesthesia syndro 1/29 (3.4%) 1 0/30 (0%) 0
    Periorbital edema 0/29 (0%) 0 1/30 (3.3%) 3
    Pruritus 0/29 (0%) 0 2/30 (6.7%) 2
    Rash acneiform 0/29 (0%) 0 2/30 (6.7%) 3
    Rash maculo-papular 1/29 (3.4%) 1 5/30 (16.7%) 33
    Rash on face 0/29 (0%) 0 1/30 (3.3%) 2
    Skin ulceration 0/29 (0%) 0 1/30 (3.3%) 2
    Telangiectasia 0/29 (0%) 0 1/30 (3.3%) 2
    Tenderness/Redness on Hands 0/29 (0%) 0 1/30 (3.3%) 1
    cold sores 1/29 (3.4%) 1 0/30 (0%) 0
    inflamed skin 0/29 (0%) 0 1/30 (3.3%) 1
    pallor 0/29 (0%) 0 1/30 (3.3%) 1
    rash 1/29 (3.4%) 2 0/30 (0%) 0
    redness of palm 0/29 (0%) 0 1/30 (3.3%) 1
    skin reddened 0/29 (0%) 0 1/30 (3.3%) 1
    skin redness: palm 0/29 (0%) 0 1/30 (3.3%) 1
    Social circumstances
    hair thinning 1/29 (3.4%) 1 0/30 (0%) 0
    Surgical and medical procedures
    Port-A-Cath insertion 1/29 (3.4%) 1 0/30 (0%) 0
    Vascular disorders
    Flushing 0/29 (0%) 0 6/30 (20%) 10
    Hot flashes 1/29 (3.4%) 1 0/30 (0%) 0
    Hypertension 17/29 (58.6%) 50 15/30 (50%) 55
    Hypotension 3/29 (10.3%) 3 6/30 (20%) 11

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Jeff Longmate, Ph.D.
    Organization City of Hope
    Phone 626-218-2478
    Email jlongmate@coh.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01727089
    Other Study ID Numbers:
    • NCI-2012-02206
    • NCI-2012-02206
    • PHII-121
    • PhII-121
    • 9144
    • N01CM00038
    • N01CM00039
    • N01CM00071
    • N01CM00099
    • P30CA033572
    First Posted:
    Nov 15, 2012
    Last Update Posted:
    Aug 28, 2018
    Last Verified:
    Jul 1, 2018